The proposed research will develop primary muscle cell cultures and muscle cell lines as a system to study the role of glucocorticoid hormones in promoting development of differentiating tissues. The effect of glucocorticiods on morphological, biochemical and physiological parameters of muscle development will be defined. The isolation of glucocorticoid resistant mutants from existing muscle cell lines will help to dissect the role of glucocorticoids in muscle development. Mutants will also be valuable in determining if malfunction of glucocorticoid regulatory mechanisms results in abnormal development of differentiating muscle or in specific genetic diseases. Methods developed will define the domain of response of muscle to glucocorticoids. These studies will analyze the concept that glucocorticoids are in fact pleiotropic effectors. This index of gene responsiveness to glucocorticoid stimulation of repression will be useful in dissecting the mechanism of glucocorticoid action. The glucocorticoid domian of other responsiveness tissues such as lung, neural retina, pancreas, and adipocytes will be described for comparative purposes. Since glucocorticoid receptors are ubiquitous in differentiating tissues, comparative studies might explicate a common function of the hormone in all developing tissues. These common functions might be mandatory for hormone responsiveness. The analysis of the mode of action of glucocorticioid hormones in developing tissues will be greatly advanced by such comparative studies.